Data_Sheet_8_Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease.XLSX

Background: Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood.
Methods: To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. In-silico profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways.
Results: Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways.
Conclusions: In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.

背景：炎症性肠病（Inflammatory Bowel Disease, IBD）是一类多因素介导的胃肠道慢性炎症性疾病，涵盖克罗恩病（Crohn's disease, CD）与溃疡性结肠炎（Ulcerative Colitis, UC）。尽管二者在病理生物学特征与疾病症状上存在相似性，但克罗恩病与溃疡性结肠炎实为两种独立疾病，且治疗应答表现各异。尽管现有研究已证实炎症性肠病与肠道菌群的显著改变密切相关，但针对克罗恩病、溃疡性结肠炎所引发的肠道菌群组具体变化，以及由此对宿主产生的相关代谢影响，目前仍有待深入阐明。
方法：为填补这一研究空白，本研究依托QIIME2、DIAMOND及STAMP生物信息学平台，对来自5个不同国家的5个炎症性肠病患者队列的肠道菌群组数据开展了大规模无偏倚元分析（Meta-Analysis）。同时通过代谢通路的计算机模拟分析（in silico profiling）与群落代谢建模，鉴定出与疾病特异性相关的代谢通量及信号通路关联。
结果：本研究结果显示，在较高的系统发育层级上，健康个体与炎症性肠病患者的肠道菌群群落结构具有高度保守性。但在分类学等级为目级及更低的层级中，二者存在显著的疾病特异性群落改变。类似地，本研究鉴定出克罗恩病与溃疡性结肠炎中代谢通路的富集差异，其中除其他代谢通路外，还包括与氨基酸、聚糖生物合成及代谢相关的富集通路。
结论：综上，本研究凸显了利用肠道菌群以加深对克罗恩病与溃疡性结肠炎病因学的理解，并开发新型预后及治疗策略的应用前景。